While the immune system is essential for fighting off infections, the immune response to infections (foreign antigens) and the immune response to molecules produced in the body (autologous antigens) may result in numerous diseases, i.e., immune system-mediated diseases. Immune system-mediated diseases may be either B cell-mediated (i.e., antibody-mediated) or T cell-mediated. Additionally, immune system-mediated diseases may be caused by immune complexes formed between antibodies and antigens (either foreign or autologous). Many immune system-mediated diseases involve an undesirable inflammatory response, e.g., diseases which include rheumatoid arthritis, chronic hepatitis, Crohn's Disease, psoriasis, vasculitis, and the like.
Existing therapies for immune system-mediated diseases, particularly immune system-mediated diseases resulting in an undesirable inflammatory response, such as rheumatoid arthritis, are inadequate. Most immune system-mediated diseases are chronic conditions which require the prolonged administration of drugs. Accordingly, it is important to employ relatively non-toxic drugs. However, many compounds used for the treatment of autoimmune diseases, e.g., steroids and non-steroidal anti-inflammatory compounds, have significant toxic side effects that become apparent after long-term use. Additionally, immunosuppressive drugs have been used to treat autoimmune responses. Such immunosuppressive drugs, e.g., cyclosporin A and azathioprine, are relatively non-specific and have the adverse effect of weakening the entire immune system, thereby leaving a patient susceptible to infectious disease.
The oral administration of compounds has been shown to induce immune tolerance with respect to the ingested compound and compounds structurally related to the ingested compound. It has been suggested that the phenomenon of oral tolerance induction be adapted as a method of treating autoimmune disease. PCT publication WO 95/10301 describes the use of oral ingested cholera toxin conjugates to decrease a delayed hypersensitivity reaction and control experimental autoimmune encephalitis in mouse models.
In view of the shortcomings of existing techniques for treating chronic immune system-mediated diseases, it is of interest to provide new methods and compositions for the treatment of immune system-mediated diseases, including rheumatoid arthritis. Methods described herein employ one or more collagens and/or collagen derivatives so as to reduce or eliminate an immune response that is important for the pathogenesis of rheumatoid arthritis. The methods and formulations are designed to induce tolerance to antigens involved in the disease process.